In the United States, cardiovascular disease is the predominant cause of death among men and women, accounting for more than 40% of all deaths. Blood vessel replacement is a common treatment for many vascular diseases, with over 500,000 vascular grafts (vein grafts, and synthetic grafts) used in bypass procedures each year. Vein grafts, which are taken from a host, are limited by availability, extra surgeries, and morbidity. Additionally, current small-diameter synthetic grafts are ineffective because they are prone to frequent clogging due to thrombogenesis. The goal of this project is to integrate the knowledge and tools of bioengineering, nanotechnology, biomaterials and vascular biology in order to develop and characterize nanofibrous vascular grafts that are acellular, biodegradable, promote endothelialization, have long term patency, and are available off-the-shelf. Preliminary results from our lab have shown that biodegradable nanofibrous vascular grafts have the potential for excellent extracellular, matrix (ECM) remodeling, cell infiltration/organization. The nanofibers can mimic native matrix fibrils in the vascular wall which promotes endothelial cell (EC) migration and triggers re-endothelialization. Additionally, the large surface area to volume ratio of nanofibrous grafts allows for efficient and high capacity loading of bioactive molecules. The loading of bioactive molecules could serve as a drug delivery mechanism to further promote re-endothelialization of vascular grafts. We hypothesize that the chemical and geometrical features of nanofibrous grafts can be engineered to develop vascular grafts that efficiently promote endothelialization and have long term patency. Two specific aims are proposed: 1. To investigate the effects of nanofiber diameter on EC migration and endothelialization in nanofibrous vascular grafts 2. To develop and characterize nanofibrous vascular graft with VEGF modification to further promote endothelialization. [unreadable] [unreadable] [unreadable]